[0001] This invention relates to a sustained release device for producing continuous administration
of a biologically active agent or composition in the reticulorumen of a ruminant animal,
especially to provide for the controlled release of such an agent or composition over
a prolonged period to range-fed ruminants, such as ,cattle or sheep.
[0002] U.
S, Patent No. 4,251,506 discloses controlled- release compositions for administration
of therapeutic agents, including weight-gain promoting agents. These compositions
generally comprise one or more active agents embodied in a solid composition, such
as a waxy carrier or surfactant. The agents may be dispersed throughout the composition
either uniformly or in spaced layers. The patent proposes to enclose a solid plug
or charge of the composition in a tubular capsule having a restricted opening at one
end and a coil spring container at the other end to resiliently urge the plug or charge
toward such opening. The capsule is administered into the reticulorumen, where the
composition containing the active agent will be delivered or eroded into or absorbed
by the ruminal fluid at the end opening of the capsule over an extended period. To
retain the capsule in the rumen and prevent it from being regurgitated, the capsule
of the patent is provided with a pair of resilient arms attached at an acute angle
of approximately 45° to the body of the capsule at the delivery end thereof, and it
is contemplated that these will be resiliently bent against the tubular body of the
capsule when it is inserted through the esophagus of the animal to the rumen, and
that such arms will then spring outward to stand at their normal acute angle of approximately
45°, like the barbs of an arrowhead, to retain the capsule in the rumen. Example 10
of the patent reports an experiment in which the growth stimulant monensin sodium
was administered to Hereford heifers to produce a substantial weight gain over a trial
period of sixty-three days. The patent discloses a capsule with its resilient arms
at the open or delivery end of the capsule, but it is understood that the patentee
has also used capsules on which the angular arms were attached to the closed end of
the capsule opposite from the delivery end.
[0003] European Patent Application 62391 discloses a sustained release device for ruminants
which has a steel ball at one end of the device to keep it in the rumen. However,
it is necessary to keep the weighted device, or steel ball, from moving within its
housing; and, in this European Patent Application disclosure, the means for doing
this involves entrapment of the ball between an interior end and the actual drug that
is to be dispensed on a sustained basis. Its drug release rate is dependent on a series
of partitions instead of a spring and rumen fluid softening matrix concept.
[0004] It is an object of the present invention to provide an improved device and combination
thereof with a medicament-containing charge which will provide more certain and longer
lasting retention of the device in the reticulorumen, and will also facilitate oral
administration of the device through the esophagus. It is a further object of the
invention to provide better control of administration of the composition, with more
uniform administration of the medicament over long periods.
[0005] In accordance with the invention, the drug dispensing-device utilizes a cylindrical
housing made of plastic material and which has two sections that can be coupled together.
One of these sections has a closed end and the other section has a pair of open ends,
one of which is coupled to the first section. The other end of the first section has
a drug restraining means such as a restricted opening through which a drug matrix
disperses upon coming into contact with the rumen fluid. The drug matrix is kept in
constant sealing relationship with this restricted opening by a helical coil spring
that is positioned between the closed end of the second section and a piston that
is in contact with the drug. A cylindrical weight is maintained within this helical
coil spring and has an annular groove that couples it to an annular retaining ring
in the housing. Thus, the weight is trapped in a fixed position regardless of the
amount of drug that remains in the capsule.
[0006] The present invention concerns a drug dispensing device for use in the reticulorumen
of an animal comprising:
a cylindrical capsule formed of inert plastic material, said capsule having first
and second hollow sections,
said first capsule section being of an elongated cylindrical configuration with a
first open end and having a drug matrix restraining means,
said first section having a second open end opposite said first open end and formed
with a coupling means,
said second capsule section having a closed end and an opposing open end with coupling
means connecting it in sealed relationship to said first capsule section,
a cylindrical weight and a spring positioned within said capsule,
a rumen fluid dissolvable or dispersible solid drug matrix of cylindrical configuration
positioned within the interior of said capsule's first section,
said spring being biased to urge the distal end of said drug matrix against said drug
matrix restraining means and toward said first capsule section's first open end.
[0007] The accompanying drawing illustrates the invention and shows the preferred embodiment
exemplifying the best mode of carrying out the invention as presently perceived. In
such drawings:
Fig.- 1 is a substantially full-scale longitudinal section of a capsule in accordance with
the invention;
Fig. 2 is a perspective view of the piston in the capsule of Fig. 1;
Fig. 3 is a longitudinal section of Fig. 2;
Fig. 4 is a perspective view of a second embodiment of the capsule's piston; and
Fig. 5 is a longitudinal section of Fig. 4.
[0008] Referring to Fig. 1 of the drawing, capsule 11 is of cylindrical configuration and
formed from an inert plastic material such as polyethylene or polypropylene. It is
to be noted that this capsule may be in the rumen of the animal for more than 200
days, and it is essential that it not be affected by the rumen fluid. Capsule 11 has
a long first section 13 and a relatively short second section 15. A cylindrical shaped
drug matrix 17 is contained within the first section and a cylindrical weight 19 occupies
approximately the other half of the capsule. End 20 of weight 19 is preferably dimensioned
to achieve a close fitting inside closed end 16 of section-15. A helical coil spring
21 encircles weight 19 and, at one end 22, abuts a piston 23. Weight 19 has a groove
25, which is in engagement with an annular ridge 27 that extends from the inner surface
of section 15. Referring to Figs. 2 and 3, piston 23 can also be made of the same
material as the capsule sections. Thus, piston 23 can be molded and has a relatively
thin and outwardly extending skirt 29. The closed end of the piston has a contact
surface 30 which is slightly convex.
[0009] The specific composition of drug matrix 17 will vary depending upon the nature of
the active agent and in one embodiment may comprise the drug monensin sodium. The
drug matrix is formed into a relatively solid but rumen fluid dispersible composition
in order to administer the drug, to range animals over a prolonged period of approximately
200 days. The drug may also be many other substances such as an anthelmintic, other
types of growth stimulants, vitamins and trace minerals. The end 32 of the drug matrix,
adjacent opening 33 of the capsule, is exposed to ruminal temperature and fluid after
the capsule is orally administered and resides in the animal's reticulorumen. This
causes the solid composition of the drug matrix to weaken after which the active agent
will be discharged into the ruminal fluid at a rate determined by controlling factors
such as the nature of the composition and the configuration of opening 33. As the
drug matrix 17 continues to disperse drug at opening 33, its length will be reduced.
However, it is essential that the drug's end maintain its sealing relationship with
the converging annular flange 34 that defines opening 33. Otherwise, rumen fluid will
tend to seep down along the sides of the drug and create a different rate of delivery
than can be maintained by limiting exposure to the area in opening 33. It is spring
21, in combination with piston 23, which maintains this sealing relationship. Spring
21 is in a compressed condition since its unstressed length will be at least twice
the length of the capsule. Thus, the piston 23 is urged against drug matrix 17 by
spring 21, and the exposed end of matrix 17 is continually forced against the annular
flange 34 to effect a sealing relationship between them.
[0010] Keeping in mind that the animal, such as a steer, grazes on the rangelands and is
quite active, it is essential that the capsule 13 be retained in the reticuloruman
for the duration of drug delivery to avoid accidental displacement through regurgitation.
It has been found that a minimum density of approximately 1.6 will enable a high percent
of capsules of the described size to remain retained in the rumen of the animals.
Weight 19, which is approximately 212 inches long, weighs 6.8 ounces (6.35 cm long,
weighs 192.78g). It is maintained in an immobile position within capsule 13 by the
close fitting of its end 20 within closed end 16 of section 15 and an interior annular
retaining ring or ridge 27 that interlocks with annular groove 25 of the weight. Its
other end is maintained within piston 23. In this preferred embodiment the density
is 2.2.
[0011] Piston 23 in the preferred embodiment has an outwardly extending tapered flange 29,
which maintains a sealing relationship with the interior wall of capsule section 13.
This is provided to prevent rumen fluid from entering through vents 31 and attacking
portions other than face 32 of drug matrix 17. Four vents 31 have been provided in
order to prevent the forming of negative pressure within section 13. Otherwise drug
matrix 17, as it reduces in its length, would be creating a partial vacuum in the
back side of section 13 and section 15 since it is snugly contained in the cylindrical
wall of section 15. If such a partial vacuum is formed the payout rate of drug in
matrix 17 could be affected to the extent of producing inconsistent results. Piston
23 is also provided with a convex head 30 in order to cope with possible bubble formation
between it and the inner end of drug matrix 17.
[0012] Such bubbles may be formed as a result of silicone liquid that is first introduced
into the capsule prior to loading it with drug matrix 17. This silicone enables the
drug matrix 17 to maintain its capability of sliding against the inner surface of
section 13. However, it has been found that on occasion the silicone liquid and air
will become entrapped between a flat surfaced piston and the inner end of drug matrix
17. This can tend to have an adverse effect on the dispersing rate of the drug and
is believed to result from a less than complete seal against flange 34 due to the
variable compression effect of the bubbles. Domed surface 30 allows displacement of
such bubbles.
[0013] Insertion of a capsule into the reticulorumen of a steer is conveniently done with
an administration tool comprising a tubular barrel having an open end -adapted to
receive a capsule 11. The barrel of the tool is mounted on a tube having a handle
portion by which the barrel can be manipulated through the mouth of the animal to
place the end of the capsule 11 in the esophagus. The tube contains a thrust rod having
a plunger at its forward end and a thrust knob at its outer end by which the plunger
head can be advanced to discharge the capsule 11 from the barrel into the esophagus.
When the weighted capsule is thus discharged partway into the esophagus, the capsule
will then move on through the esophagus into the rumen. Tools of this general description
have been used to insert boluses and capsules of other configurations and can readily
be redesigned to apply capsule 11.
[0014] In assembling the capsule, approximately 5 cc of a lubricant such as silicone liquid
is introduced into capsule section 13. Drug matrix 17 is then inserted through its
larger open end until it is seated against flange 34. Piston 23 and spring 21 are
then inserted into section 13 to butt against the inner end of drug matrix 17. Section
15 may then be snapped onto weight 19 and weight 19 is inserted into spring 21. This
assembly is then coupled to section 13 by means of innerfitments 35 and 36. In addition,
the capsule may be sonically welded at the junction line of sections 13 and 15. A
removable label seal may be placed on the flanged end 34, preferrably prior to adding
the liquid lubricant. The capsule is now ready for use.,
[0015] In the second embodiment of Figs. 4 and 5, piston 37 utilizes a flat surface or head
38 and a flat non-tapered wall 39. Consequently, it does not maintain a sealing relationship
with the inner wall of section 13. Any bubbles initially entrapped between surface
38 and the drug will travel radially outward to the wall of section 13 and beyond
the piston's wall 39.
1. A drug dispensing device for use in the reticulorumen of an animal comprising:
a cylindrical capsule formed of inert plastic material, said capsule having first
and second hollow sections,
said first capsule section being of an elongated cylindrical configuration with a
first open end and having a drug matrix restraining means,
said first section having a second open end opposite said first.open end and formed
with a coupling means,
said second capsule section having a closed end and an opposing open end with coupling
means connecting it in sealed relationship to said first capsule section,
a cylindrical weight and a spring positioned within said capsule,
a rumen fluid dissolvable or dispersible solid drug matrix of cylindrical configuration
positioned within the interior of said capsule's first section,
said spring being biased to urge the distal end of said drug matrix against said drug
matrix restraining means and toward said first capsule section's first open end.
2. A drug dispensing device in accordance with claim 1 in which said drug matrix restraining
means comprises a converging annular flange defining said first section's first opening.
3. A drug dispensing device in accordance with claim 2 in which said solid drug matrix
is snugly contained in the cylindrical wall of said first capsule section.
4. A drug dispensing device in accordance with claim 3 in which said weight is immobilized
within said capsule.
5. A drug dispensing device in accordance with claim 4 in which one end of said weight
is in close fitment with the cylindrical wall of said second capsule section.
6. A drug dispensing device in accordance with claim 3 in which said cylindrical weight
has a circumferential portion engaged with an interior retaining means in said capsule.
7. A drug dispensing device in accordance with claim 6 in which the second section
of said capsule has an annular retaining ring which is seated in an annular groove
of said cylindrical weight.
8. A drug dispensing device in accordance with claim 7 in which said weight is encircled
by said spring which is of helical configuration.
9. A drug dispensing device in accordance with claim 8 in which a piston is positioned
between said drug matrix and the adjacent end of said spring with a cylindrical side
wall extending over said adjacent spring end and in close sliding contact with the
interior wall of said capsule.
10. A drug dispensing device in accordance with claim 9 in which said piston has an
outwardly extending tapered flange in sealing relationship with said first section's
cylindrical wall and in which said section has a vent hole.